Neurotransmitters are chemicals existing in the body, which execute the transfer of signals between neurons and target cells. After a neurotransmitter is released from a nerve terminal, it is actively transported back to the presynaptic nerve terminal by a specific reuptake transporter system. This reuptake mechanism controls the precise concentration and duration of neurotransmitter present in the synaptic space, and in turn controls the extent of stimulation of the target cell (for review, see Mol. Endo. 1993, 7, 1517–1529).
The amino acid glycine is a major neurotransmitter within the central nervous system (CNS) of vertebrates, functioning at both inhibitory and excitatory synapses. The synaptic levels of glycine are controlled by high affinity uptake systems (transporters) and two such transporters, GlyT1 (Neuron 1992, 8, 927–935) and GlyT2 (FEBS Lett. 1998, 439, 334–340), have recently been cloned.
The GlyT1 transporter is closely associated with the excitatory system in which glycine and/or D-serine acts as a co-agonist for the glutamate receptors (Nature 1987, 325, 529–531). The GlyT2 transporter is closely associated with the inhibitory system mediated through the strychnine-sensitive glycine receptor (ssGlyR) and is assumed to control the level of glycine in the synaptic space associated with this receptor (J. Neurochem. 1995, 65, 2800–2803). This inhibitory system is almost entirely confined to the spinal cord and hindbrain, where it participates in a variety of motor and sensory functions.
Selective inhibitors of the Glycine-T2 transporter increase the synaptic glycine level and in turn alter the ssGlyR function. Such compounds are useful as muscle relaxant, anesthetic and analgesic agents.